Brinzolamide/Brimonidine Combination vs Brimonidine 0.2% in the Prevention of IOP Rise After Nd-YAG Laser Capsulotomy

• Sponsor: University Hospital of Patras (Other)
• Overall Status: Completed
• CT.gov ID: NCT03192826
• Collaborator: (none)
• Enrollment: 79
• Location: 1
• Arms: 3
• Actual Duration (Months): 12.6
• Patients Per Site Per Month: 6.3

Study Details

Study Description

Brief Summary

To compare the efficacy of a Brinzolamide/Brimonidine fixed combination (FC) with Brimonidine 0.2% in preventing intraocular pressure (IOP) elevations after neodymium: yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy.

Condition or Disease	Intervention/Treatment	Phase
Posterior Capsule Opacification; Ocular Hypertension	Drug: Brinzolamide/Brimonidine FC; Drug: Brimonidine 0.2%; Drug: Artificial tears	Phase 4

Detailed Description

In this prospective, randomized, double masked clinical trial, patients scheduled to undergo Nd:YAG laser posterior capsulotomy for posterior capsule opacification are randomized in 3 groups. The Brimonidine group receives 1 drop of Brimonidine 0.2%. The Brinzolamide/Brimonidine group receives 1 drop of Brinzolamide 1%/Brimonidine 0.2% fixed combination. The Control group receives artificial tears. All groups are administered a single drop instillation, approximately one hour before Nd:YAG application. Intraocular pressure measurements are performed before treatment (baseline) and at the 1, 3, 24 hours and 1 week post treatment.

Dexamethasone ophthalmic drops are prescribed q.i.d. for one week after the procedure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a prospective, randomized, double masked comparative studyThis is a prospective, randomized, double masked comparative study
• Masking: Double (Participant, Investigator)
• Masking Description: Patients are masked to their assignment by covering the labels on the bottles of the drugs administered The investigator responsible for the measurement of the intraocular pressure is also masked to the intervention administered to each patient.
• Primary Purpose: Prevention
• Official Title: Study of the Efficacy of Brinzolamide 1% Plus Brimonidine 0.2% Versus Brimonidine 0.2% in the Prevention of Intraocular Pressure Rise After Nd-YAG Laser Capsulotomy
• Actual Study Start Date: Jun 20, 2016
• Actual Primary Completion Date: Jul 8, 2017
• Actual Study Completion Date: Jul 8, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Brinzolamide/Brimonidine FC 1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy	Drug: Brinzolamide/Brimonidine FC; 1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy; Other Names: SIMBRINZA (brinzolamide/brimonidine 1%/0.2%), Alcon Lab. Ltd
Active Comparator: Brimonidine 0.2% 1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy	Drug: Brimonidine 0.2%; 1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy; Other Names: ALPHAGAN (brimonidine tartrate 0.2%) Allergan Pharm. Ltd
Placebo Comparator: Artificial tears 1 drop of artificial tears 1 hour before Nd-YAG capsulotomy	Drug: Artificial tears; 1 drop of artificial tears 1 hour before Nd-YAG capsulotomy; Other Names: TEARS NATURALE EY.DRO.SOL 0.1%+0.3% Alcon Laboratories Ltd

Outcome Measures

Primary Outcome Measures

1. Intraocular Pressure (IOP) at 1 Hour After Nd-YAG Posterior Capsulotomy [1 hour]

   Comparison of intraocular pressure at 1 hour after Nd-YAG posterior capsulotomy compared to Baseline IOP

2. Intraocular Pressure (IOP) at 3 Hours After Nd-YAG Posterior Capsulotomy [3 hours]

   Comparison of intraocular pressure at 3 hours after Nd-YAG posterior capsulotomy compared to Baseline IOP

3. Intraocular Pressure (IOP) at 24 Hourw After Nd-YAG Posterior Capsulotomy [24 hours]

   Comparison of intraocular pressure at 24 hours after Nd-YAG posterior capsulotomy compared to Baseline IOP

4. Intraocular Pressure (IOP) at 1 Week After Nd-YAG Posterior Capsulotomy [1 week]

   Comparison of intraocular pressure at 1 week after Nd-YAG posterior capsulotomy compared to Baseline IOP

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• patients scheduled to undergo laser posterior capsulotomy due to posterior capsule opacification (PCO) after uneventful phacoemulsification cataract extraction with implantation of posterior chamber intraocular lenses (IOL/PC).

Exclusion Criteria:

• baseline IOP greater than 21mmHg

• glaucomatous eyes, already under treatment with anti glaucomatic medications

• intraocular surgery except for uncomplicated cataract surgery

• previous photorefractive surgery

• active ocular inflammation or infection

• patients under systemic administration of medications known to affect IOP

• patients with severe respiratory or cardiovascular disease

• pregnant or breast feeding women, and individuals with known hypersensitivity or contraindication for administration of the medications tested

• a measurement of IOP > 30 mmHg at any time point of the study, or an increase from baseline >20 mmHg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital of Patras	Patra	Achaia	Greece	26504

Sponsors and Collaborators

• University Hospital of Patras

Investigators

• Study Director: Constantinos Georgakopoulos, MD, PhD, University Hospital of Patras

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 24, 2016

More Information

Publications

None provided.

• Responsible Party: Constantinos D. Georgakopoulos, MD, PhD, MD, PhD, Associate Professor of Ophthalmology, Univerisity of Patras, University Hospital of Patras
• ClinicalTrials.gov Identifier: NCT03192826
• Other Study ID Numbers: 8393 / 26- 4- 2016
• First Posted: Jun 20, 2017
• Last Update Posted: Jul 16, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Constantinos D. Georgakopoulos, MD, PhD, MD, PhD, Associate Professor of Ophthalmology, Univerisity of Patras, University Hospital of Patras: Nd-YAG capsulotomy; ocular hypertension; brimonidine; brinzolamide
• Additional relevant MeSH terms: Ocular Hypertension; Capsule Opacification; Hypertension; Brimonidine Tartrate; Lubricant Eye Drops; Dipivefrin; Brinzolamide

Study Results

Participant Flow

Arm/Group Title	Brinzolamide/Brimonidine FC	Brimonidine 0.2%	Artificial Tears
Arm/Group Description	1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy Brinzolamide/Brimonidine FC: 1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy	1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy Brimonidine 0.2%: 1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy	1 drop of artificial tears 1 hour before Nd-YAG capsulotomy Artificial tears: 1 drop of artificial tears 1 hour before Nd-YAG capsulotomy
Period Title: Overall Study
STARTED	27	27	25
COMPLETED	27	27	25
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Brinzolamide/Brimonidine FC	Brimonidine 0.2%	Artificial Tears	Total
Arm/Group Description	1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy Brinzolamide/Brimonidine FC: 1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy	1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy Brimonidine 0.2%: 1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy	1 drop of artificial tears 1 hour before Nd-YAG capsulotomy Artificial tears: 1 drop of artificial tears 1 hour before Nd-YAG capsulotomy	Total of all reporting groups
Overall Participants	27	27	25	79
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.9 (6.3)	65.2 (6.0)	67.6 (3.9)	65.5 (5.8)
Sex: Female, Male (Count of Participants)
Female	13 48.1%	11 40.7%	13 52%	37 46.8%
Male	14 51.9%	16 59.3%	12 48%	42 53.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	27 100%	27 100%	25 100%	79 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Greece	27 100%	27 100%	25 100%	79 100%

Outcome Measures

1. Primary Outcome

Title	Intraocular Pressure (IOP) at 1 Hour After Nd-YAG Posterior Capsulotomy
Description	Comparison of intraocular pressure at 1 hour after Nd-YAG posterior capsulotomy compared to Baseline IOP
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

Comparison of intraocular pressure at 1 hour after Nd-YAG posterior capsulotomy compared to Baseline IOP

Arm/Group Title	Brinzolamide/Brimonidine FC	Brimonidine 0.2%	Artificial Tears
Arm/Group Description	1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy Brinzolamide/Brimonidine FC: 1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy	1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy Brimonidine 0.2%: 1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy	1 drop of artificial tears 1 hour before Nd-YAG capsulotomy Artificial tears: 1 drop of artificial tears 1 hour before Nd-YAG capsulotomy
Measure Participants	27	27	25
Baseline	15.6 (1.5)	15.7 (1.5)	15.2 (1.9)
1 hour	13.7 (2.0)	14.7 (3.7)	19.5 (2.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brinzolamide/Brimonidine FC, Brimonidine 0.2%, Artificial Tears
	Comments
	Type of Statistical Test	Equivalence
	Comments	The SPSS statistical package version 23.0 (Statistical Package for the Social Sciences, version 23.0, SSPS Inc. Chicago, IL, USA) was used for statistical analysis.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments	Repeated measures ANOVA was used to compare parametric values with Bonferroni post hoc test for within group comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	the reported p-value was calculated, and is not attempting to indicate the threshold for statistical significance

2. Primary Outcome

Title	Intraocular Pressure (IOP) at 3 Hours After Nd-YAG Posterior Capsulotomy
Description	Comparison of intraocular pressure at 3 hours after Nd-YAG posterior capsulotomy compared to Baseline IOP
Time Frame	3 hours

Outcome Measure Data

Analysis Population Description

Comparison of intraocular pressure at 3 hours after Nd-YAG posterior capsulotomy compared to Baseline IOP

Arm/Group Title	Brinzolamide/Brimonidine FC	Brimonidine 0.2%	Artificial Tears
Arm/Group Description	1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy Brinzolamide/Brimonidine FC: 1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy	1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy Brimonidine 0.2%: 1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy	1 drop of artificial tears 1 hour before Nd-YAG capsulotomy Artificial tears: 1 drop of artificial tears 1 hour before Nd-YAG capsulotomy
Measure Participants	27	27	25
Baseline	15.6 (1.5)	15.7 (1.5)	15.2 (1.9)
3 hours	12.7 (1.5)	14.7 (3.7)	19.5 (2.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brinzolamide/Brimonidine FC, Brimonidine 0.2%, Artificial Tears
	Comments
	Type of Statistical Test	Equivalence
	Comments	The SPSS statistical package version 23.0 (Statistical Package for the Social Sciences, version 23.0, SSPS Inc. Chicago, IL, USA) was used for statistical analysis.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments	Repeated measures ANOVA was used to compare parametric values with Bonferroni post hoc test for within group comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	the reported p-value was calculated, and is not attempting to indicate the threshold for statistical significance

3. Primary Outcome

Title	Intraocular Pressure (IOP) at 24 Hourw After Nd-YAG Posterior Capsulotomy
Description	Comparison of intraocular pressure at 24 hours after Nd-YAG posterior capsulotomy compared to Baseline IOP
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Comparison of intraocular pressure at 24 hours after Nd-YAG posterior capsulotomy compared to Baseline IOP

Arm/Group Title	Brinzolamide/Brimonidine FC	Brimonidine 0.2%	Artificial Tears
Arm/Group Description	1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy Brinzolamide/Brimonidine FC: 1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy	1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy Brimonidine 0.2%: 1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy	1 drop of artificial tears 1 hour before Nd-YAG capsulotomy Artificial tears: 1 drop of artificial tears 1 hour before Nd-YAG capsulotomy
Measure Participants	27	27	25
Baseline	15.6 (1.5)	15.7 (1.5)	15.2 (1.9)
24 hours	14.6 (1.1)	15.5 (1.7)	15.8 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brinzolamide/Brimonidine FC, Brimonidine 0.2%, Artificial Tears
	Comments
	Type of Statistical Test	Equivalence
	Comments	The SPSS statistical package version 23.0 (Statistical Package for the Social Sciences, version 23.0, SSPS Inc. Chicago, IL, USA) was used for statistical analysis.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments	Repeated measures ANOVA was used to compare parametric values with Bonferroni post hoc test for within group comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	the reported p-value was calculated, and is not attempting to indicate the threshold for statistical significance

4. Primary Outcome

Title	Intraocular Pressure (IOP) at 1 Week After Nd-YAG Posterior Capsulotomy
Description	Comparison of intraocular pressure at 1 week after Nd-YAG posterior capsulotomy compared to Baseline IOP
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

Comparison of intraocular pressure at 1 weekafter Nd-YAG posterior capsulotomy compared to Baseline IOP

Arm/Group Title	Brinzolamide/Brimonidine FC	Brimonidine 0.2%	Artificial Tears
Arm/Group Description	1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy Brinzolamide/Brimonidine FC: 1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy	1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy Brimonidine 0.2%: 1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy	1 drop of artificial tears 1 hour before Nd-YAG capsulotomy Artificial tears: 1 drop of artificial tears 1 hour before Nd-YAG capsulotomy
Measure Participants	27	27	25
Baseline	15.6 (1.5)	15.7 (1.5)	15.2 (1.9)
1 week	15.5 (1.1)	15.3 (1.5)	15.6 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brinzolamide/Brimonidine FC, Brimonidine 0.2%, Artificial Tears
	Comments
	Type of Statistical Test	Equivalence
	Comments	The SPSS statistical package version 23.0 (Statistical Package for the Social Sciences, version 23.0, SSPS Inc. Chicago, IL, USA) was used for statistical analysis.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments	Repeated measures ANOVA was used to compare parametric values with Bonferroni post hoc test for within group comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	the reported p-value was calculated, and is not attempting to indicate the threshold for statistical significance

Adverse Events

Time Frame	1month
Adverse Event Reporting Description	The same with clinicaltrials.gov Definitions
Arm/Group Title	Brinzolamide/Brimonidine FC		Brimonidine 0.2%		Artificial Tears
Arm/Group Description	1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy Brinzolamide/Brimonidine FC: 1 drop of Brinzolamide/Brimonidine FC 1 hour before capsulotomy		1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy Brimonidine 0.2%: 1 drop of Brimonidine 0.2% 1 hour before Nd-YAG capsulotomy		1 drop of artificial tears 1 hour before Nd-YAG capsulotomy Artificial tears: 1 drop of artificial tears 1 hour before Nd-YAG capsulotomy
All Cause Mortality
	Brinzolamide/Brimonidine FC		Brimonidine 0.2%		Artificial Tears
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)		0/25 (0%)
Serious Adverse Events
	Brinzolamide/Brimonidine FC		Brimonidine 0.2%		Artificial Tears
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Brinzolamide/Brimonidine FC		Brimonidine 0.2%		Artificial Tears
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)		0/25 (0%)

Limitations/Caveats

Corneal thickness was not assessed. The measurement of IOP at more time points could have provided more information regarding the effect of BBFC. We could enroll a larger group of patients in order to provide more strength in our analysis

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.